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Molecular determinants for G protein betagamma modulation of ionotropic glycine receptors.

Authors
  • Yevenes, Gonzalo E
  • Moraga-Cid, Gustavo
  • Guzmán, Leonardo
  • Haeger, Svenja
  • Oliveira, Laerte
  • Olate, Juan
  • Schmalzing, Günther
  • Aguayo, Luis G
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
Dec 22, 2006
Volume
281
Issue
51
Pages
39300–39307
Identifiers
PMID: 17040914
Source
Medline
License
Unknown

Abstract

The ligand-gated ion channel superfamily plays a critical role in neuronal excitability. The functions of glycine receptor (GlyR) and nicotinic acetylcholine receptor are modulated by G protein betagamma subunits. The molecular determinants for this functional modulation, however, are still unknown. Studying mutant receptors, we identified two basic amino acid motifs within the large intracellular loop of the GlyR alpha(1) subunit that are critical for binding and functional modulation by Gbetagamma. Mutations within these sequences demonstrated that all of the residues detected are important for Gbetagamma modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are alpha-helixes near transmembrane domains 3 and 4, near to the lipid bilayer and highly electropositive. Our results demonstrate for the first time the sites for G protein betagamma subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling.

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